Ketamine, an anesthetic added to the World Health Organization's essential medicines lists, is effective for acute pain at sub-anesthetic doses and may relieve some chronic pain. In 2019, its S-enantiomer was approved for treatment-resistant major depressive disorder. Pre-existing anxiety or depression and severe postoperative pain are risk factors for chronic postsurgical pain. This review examines ketamine's effects on biological and psychological processes underlying pain and mood disorders, focusing on non-NMDA receptor mechanisms and human trial results, to assess whether short-term ketamine can prevent acute postsurgical pain from becoming chronic.
Psilocybin and a psychedelic mushroom extract reduced compulsive marble burying and excessive self-grooming in mouse models of obsessive-compulsive disorder (OCD). A single dose of psilocybin remained effective for more than 21 days in SAPAP3-knockout mice, which model OCD and Tourette's syndrome. The mushroom extract showed slightly greater efficacy than psilocybin alone. Two novel compounds, one hallucinogenic and one non-hallucinogenic, were also effective in both mouse models. The non-hallucinogenic compound HBL20017 may offer therapeutic benefit for OCD without inducing psychedelic effects.